ABSTRACT This study, along with other studies in the CDC PFAS multi-site health study, will determine whether modelled and measured serum concentrations for per- and polyfluoroalkyl substances (PFAS) are associated with a variety of cross-sectional health outcomes in child and adult participants. In addition to the mandatory core protocol, this study will investigate associations of PFAS with weekly parental reports of child symptoms of allergy, infection, or asthma collected for up to one year after enrollment. The study includes communities surrounding the Medical Center at the University of California, Irvine, with PFAS detections in community water supplies. Exposure reconstruction will use well-characterized hydrogeological models for our local watersheds, estimated source terms for wastewater treatment plants, and utility data on well mixing and water distribution to estimate historical PFOA, PFOS, and PFHpA concentrations in community water in the study area. Models for estimating the water concentrations at participants' homes and workplaces will be validated by analysis of PFAS in tap water samples, and used to estimate historical monthly PFAS doses for each study participant. Pharmacokinetic models will be developed for perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorohexanesulfonate (PFHxS), perfluoroheptanoate (PFHpA), and perfluorobutanesulfonate (PFBS), and validated by comparison of nationwide measurements of these PFAS chemicals in public water systems, collected from 2013-2015 under EPA's Third Unregulated Contaminant Monitoring Rule, to individual serum measurements from the National Biomonitoring Program. These pharmacokinetic models and estimated doses for each participant will be used to obtain modelled serum PFAS concentrations over time for each participant. Bayesian pharmacokinetic calibration of modelled serum PFAS concentrations, and non-parametric epidemiological analysis of PFAS exposure mixtures, will also be conducted when appropriate. This study will help address the key policy question of whether people served by water systems with PFAS detections are at greater risk of adverse health effects than those who do not have PFAS in their water, after accounting for other known risk factors. It will also provide useful information regarding the extent to which PFAS in drinking water contributes to overall exposure and biomonitoring results for these chemicals in a nationally representative sample.